Lipocalin 2 promotes lung metastasis of murine breast cancer cells.

Lipocalin 2 promotes lung metastasis of murine breast cancer cells.
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DOI:
10.1186/1756-9966-27-83
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发表时间:
2008-12-12
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Yu W
Yu W
中科院分区:
其他
文献类型:
--
作者:
Shi H;Gu Y;Yang J;Xu L;Mi W;Yu W

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脂质运载蛋白2是一种铁结合蛋白,在一些人类恶性癌症中异常表达,可能在肿瘤转移中发挥重要作用。然而,脂质运载蛋白2在乳腺癌形成和转移中的作用尚未明确显示。本研究旨在探讨脂质运载蛋白2在乳腺肿瘤转移中的作用。脂质运载蛋白 2 在转移性 4T1 鼠乳腺癌细胞中过度表达。采用体外细胞增殖实验、迁移实验、侵袭实验和软琼脂实验检测脂质运载蛋白2过表达对乳腺癌细胞恶性程度的影响。使用完善的体内小鼠乳腺肿瘤模型检查肿瘤形成和转移能力。 Lipocalin 2过表达显着增强4T1细胞的体外迁移和侵袭能力以及体内肺转移能力。但 4T1 细胞中脂质运载蛋白 2 的过度表达并不影响细胞增殖和体外贴壁依赖性生长,也不影响体内原发肿瘤重量。进一步的研究表明,PI3K/Akt通路的抑制可能是脂质运载蛋白2过表达诱导乳腺癌迁移/侵袭的促进机制。这些结果阐明了lipocalin 2可以通过抑制PI3K/Akt通路促进4T1细胞的肺转移,表明lipocalin 2是治疗乳腺癌的潜在靶点。
Lipocalin 2, an iron binding protein, is abnormally expressed in some malignant human cancers and may play an important role in tumor metastasis. However, the roles of lipocalin 2 in breast cancer formation and metastasis have not been clearly shown. This study aimed to investigate the roles of lipocalin 2 in breast tumor metastasis. Lipocalin 2 was overexpressed in the metastatic 4T1 murine mammary cancer cells. The effects of lipocalin 2 overexpression on the malignancy of breast cancer cells were examined using cell proliferation assay, migration assay, invasion assay, and soft agar assay in vitro. Tumor formation and metastasis abilities were examined using a well established mouse mammary tumor model in vivo. Lipocalin 2 overexpression significantly enhanced the migration and invasion abilities of 4T1 cells in vitro, and lung metastasis in vivo. But overexpression of lipocalin 2 in 4T1 cells didn't affect cell proliferation and anchorage-independent growth in vitro, and primary tumor weight in vivo. Further studies demonstrated that the inhibition of the PI3K/Akt pathway could be a causative mechanism for the promotion of breast cancer migration/invasion induced by lipocalin 2 overexpression. These results clarified that lipocalin 2 could promote lung metastasis of 4T1 cells through the inhibition of the PI3K/Akt pathway, suggesting that lipocalin 2 was a potential target for therapy of breast cancer.
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